Adam M. Brufsky, MD, PhD
Approximately 1 million breast cancer cases are diagnosed annually worldwide, with about 17% (n = 170,000) being triple-negative breast cancer (TNBC).1
Most TNBCs, about 75%, have been considered “basal-like,” meaning their expression signature has been shown to be comparable to that of the basal/myoepithelial cells of the breast, with transcriptomic characteristics similar to tumors arising in BRCA1 germline mutation carriers;2
however, more recently, genomic analysis has shown TNBCs to have substantial transcriptional, mutational, and copy number heterogeneity, indicating these tumors are significantly more heterogeneous than previously thought.3,4
Such findings have helped spur new developments in treating patients with TNBC, a cancer field that has seen relatively few meaningful clinical advancements since the introduction of adjuvant taxane therapy approximately 20 years ago.4
testing and other predictive biomarkers and on the promise of 2 novel treatment approaches currently under investigation for TNBC: immunotherapy and anti-body–drug conjugates.
TNBC Heterogeneity and BRCA Testing
The complexity of TNBCs is increasingly being understood as gene expression profiling is revealing more subtypes. “We’re learning over the last couple of years that these really are likely a collection of multiple different diseases,” said Brufsky. The most recent classification, which revised a widely accepted earlier classification by the same investigators, breaks them into 4 tumor-specific subtypes: 2 basal-like (BL1 and BL2), a mesenchymal (M), and a luminal androgen receptor (LAR) subtype (Table 1
When using these subtypes to assess response to neoadjuvant chemotherapy, significant differences between patient groups have been observed, with a pathological complete response (pCR) found in 41% of BL1 patients, 29% of LAR patients, and 18% of BL2 patients.5
The relevance of these subtypes has yet to be elucidated in prospective studies, and these subtypes have the potential to guide patient selection with regard to some of the newer treatments that are being investigated in clinical trials, including immunotherapy and antibody–drug conjugates.4
BL indicates basal-like; LAR, luminal androgen receptor; M, mesenchymal.
Table 1. Commonly Accepted Molecular Subtypes of TNBC Based on Gene expression Profiling
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